Stressors, emotions, and social support systems among respiratory nurses during the Omicron outbreak in China: a qualitative study.

BACKGROUND: Respiratory nurses faced tremendous challenges when the Omicron variant spread rapidly in China from late 2022 to early 2023. An in-depth understanding of respiratory nurses' experiences during challenging times can help to develop better management and support strategies. The present study was conducted to explore and describe the work experiences of nurses working in the Department of Pulmonary and Critical Care Medicine (PCCM) during the Omicron outbreak in China. METHODS: This study utilized a descriptive phenomenological method. Between January 9 and 22, 2023, semistructured and individual in-depth interviews were conducted with 11 respiratory nurses at a tertiary hospital in Wuhan, Hubei Province. A purposive sampling method was used to select the participants, and the sample size was determined based on data saturation. The data analysis was carried out using Colaizzi's method. RESULTS: Three themes with ten subthemes emerged: (a) multiple stressors (intense workload due to high variability in COVID patients; worry about not having enough ability and energy to care for critically ill patients; fighting for anxious clients, colleagues, and selves); (b) mixed emotions (feelings of loss and responsibility; feelings of frustration and achievement; feelings of nervousness and security); and (c) a perceived social support system (team cohesion; family support; head nurse leadership; and the impact of social media). CONCLUSION: Nursing managers should be attentive to frontline nurses' needs and occupational stress during novel coronavirus disease 2019 (COVID-19) outbreaks. Management should strengthen psychological and social support systems, optimize nursing leadership styles, and proactively consider the application of artificial intelligence (AI) technologies and products in clinical care to improve the ability of nurses to effectively respond to future public health crises.

Bioactive Components of Areca Nut: An Overview of Their Positive Impacts Targeting Different Organs.

Areca catechu L. is a widely cultivated tropical crop in Southeast Asia, and its fruit, areca nut, has been consumed as a traditional Chinese medicinal material for more than 10,000 years, although it has recently attracted widespread attention due to potential hazards. Areca nut holds a significant position in traditional medicine in many areas and ranks first among the four southern medicines in China. Numerous bioactive compounds have been identified in areca nuts, including alkaloids, polyphenols, polysaccharides, and fatty acids, which exhibit diverse bioactive functions, such as anti-bacterial, deworming, anti-viral, anti-oxidant, anti-inflammatory, and anti-tumor effects. Furthermore, they also display beneficial impacts targeting the nervous, digestive, and endocrine systems. This review summarizes the pharmacological functions and underlying mechanisms of the bioactive ingredients in areca nut. This helps to ascertain the beneficial components of areca nut, discover its medicinal potential, and guide the utilization of the areca nut.

Endophthalmitis in silicone oil-filled eye: A case report.

BACKGROUND: Endophthalmitis occurring in silicone oil-filled eyes is a very rare occurrence, with reported incidence rates ranging between 0.07% and 0.039%. Traditional methods of management of infectious endophthalmitis include the removal of silicone oil, washout of the vitreous cavity, administration of intravitreal antibiotics, and re-injection of silicone oil. CASE SUMMARY: Herein, we report the case of a 39-year-old man with unilateral endophthalmitis after pars plana vitrectomy and silicone oil tamponade. Intravitreal injections of full-dose antibiotics and anterior chamber washout were used to treat the patient. No signs of retinal toxicity were observed during the follow-up period. CONCLUSION: Intravitreal full-dose antibiotic injections and anterior chamber washout are promising alternatives to traditional therapies for endophthalmitis in silicone oil-filled eyes.

An interpretable model predicts visual outcomes of no light perception eyes after open globe injury.

BACKGROUND: The visual outcome of open globe injury (OGI)-no light perception (NLP) eyes is unpredictable traditionally. This study aimed to develop a model to predict the visual outcomes of vitrectomy surgery in OGI-NLP eyes using a machine learning algorithm and to provide an interpretable system for the prediction results. METHODS: Clinical data of 459 OGI-NLP eyes were retrospectively collected from 19 medical centres across China to establish a training data set for developing a model, called 'VisionGo', which can predict the visual outcome of the patients involved and compare with the Ocular Trauma Score (OTS). Another 72 cases were retrospectively collected and used for human-machine comparison, and an additional 27 cases were prospectively collected for real-world validation of the model. The SHapley Additive exPlanations method was applied to analyse feature contribution to the model. An online platform was built for real-world application. RESULTS: The area under the receiver operating characteristic curve (AUC) of VisionGo was 0.75 and 0.90 in previtrectomy and intravitrectomy application scenarios, which was much higher than the OTS (AUC=0.49). VisionGo showed better performance than ophthalmologists in both previtrectomy and intravitrectomy application scenarios (AUC=0.73 vs 0.57 and 0.87 vs 0.64). In real-world validation, VisionGo achieved an AUC of 0.60 and 0.91 in previtrectomy and intravitrectomy application scenarios. Feature contribution analysis indicated that wound length-related indicators, vitreous status and retina-related indicators contributed highly to visual outcomes. CONCLUSIONS: VisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.

Effect of Heat Treatment Parameters on the Modification of Nano Residual Austenite of Low-Carbon Medium-Chromium Steel.

The ball milling lining board operates in a harsh environment, and the current materials fail to meet the requirements for large-sized boards due to the lack of synergistic properties between impact toughness and wear resistance. To address this issue, a low-carbon medium-chromium steel with martensite and nano residual austenite phases have been designed for future use. However, the residual austenite network could decrease the properties. Heat treatment, which includes processes like quenching and tempering, has the potential to alter the morphology and quantity of nano-scale residual austenite in the steel. In this study, the influence of heat treatment parameters on the morphologies and properties of steel has been investigated to address the wide-ranging fluctuations in impact toughness affected by nano residual austenite. Furthermore, the effect of cooling transformation on the microstructure has also been examined. The research findings indicate that modifying the quenching temperature of the steel within the range of 950-1100 °C results in a microstructure comprising martensite and nano residual austenite. At all quenching temperatures, the hardness exceeds 45 HRC, and the impact toughness shows a consistent improvement with increasing quenching temperature, indicating a modification of the nano residual austenite phase. The failure mode is primarily dimple fracture, with quasi-dissociation fracture as a secondary mode. The optimal heat treatment parameters are annealing at 930 °C, oil quenching at 1050 °C, and tempering at 250 °C. Under this condition, the steel exhibits a hardness of 51 HRC and impact toughness of 40 J/cm2 and an approximate fourfold increase compared to the untreated sample.

Dendrobium mixture ameliorates hepatic injury induced by insulin resistance in vitro and in vivo through the downregulation of AGE/RAGE/Akt signaling pathway.

Dendrobium mixture (DM) is a patented Chinese herbal medicine which has been shown to ameliorate type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro. We aimed to investigate the underlying mechanism of DM as a therapeutic agent in attenuating liver steatosis in relation to type 2 diabetes mellitus (T2DM). DM (16.2 g/kg/d) was administered to db/db mice for 4 weeks. The db/m mice and db/db mice in the control and model groups were given normal saline. Additionally, DM (11.25 g/kg/d) was administered to Sprague-Dawley (SD) rats, and the serum was collected and used in an experiment involving palmitic acid (PA)-induced human liver HepG2 cells with abnormal lipid and glucose metabolism. In db/db mice, the administration of DM significantly alleviated liver steatosis, including histological damage and cell apoptosis. DM was found to prevent the upregulation of the RAGE and AKT1 proteins in liver tissues. The underlying mechanism of DM was further studied in PA-induced HepG2 cells. Post-DM administration serum from SD rats reduced lipid accumulation and regulated glucose metabolism in HepG2 cells. Consequently, it inhibited RAGE/AKT signaling and restored autophagy activity. The upregulated autophagy was associated with the mTOR-AMPK signaling pathway. Furthermore, post-DM administration serum reduced apoptosis of hepatocytes in PA-induced HepG2 cells. Our study supports the potential use of DM as a therapeutic agent for the treatment of NAFLD in T2DM. The mechanism underlying this therapeutic potential is associated with the downregulation of the AGE/RAGE/Akt signaling pathway.

CRISPR/SaCas9-based gene editing rescues photoreceptor degeneration throughout a rhodopsin-associated autosomal dominant retinitis pigmentosa mouse model.

Rhodopsin (Rho) gene mutation was considered the highest prevalent mutation in autosomal dominant retinitis pigmentosa (ADRP); however, effective therapeutics for ADRP have not been developed. The process of gene editing via the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system offers the potentiality to provide cures for dominantly inherited disorders. Herein, we generated a CRISPR/SaCas9-mediated gene reduction system to inactivate the Rho mutant, while replacing normal rhodopsin in a rhodopsin mutation mouse model. When Rho-P23H knock-in mice were administered a subretinal injection of the "reduction and replacement" system, the expression of mutant rhodopsin was reduced, and retinal function was improved. Therefore, we concluded that CRISPR/SaCas9-based "reduction and replacement" gene therapy could provide structural and functional benefits for Rho mutant ADRP, as well as new directions for future clinical research on the treatment of such gain-of-function genetic diseases.

Dendrobium mixture ameliorates type 2 diabetes mellitus with non-alcoholic fatty liver disease through PPAR gamma: An integrated study of bioinformatics analysis and experimental verification.

Dendrobium mixture (DM) is a patented Chinese herbal medicine indicated which has anti-inflammatory and improved glycolipid metabolism. However, its active ingredients, targets of action, and potential mechanisms are still uncertain. Here, we investigate the role of DM as a prospective modulator of protection against non-alcoholic fatty liver disease (NAFLD) induced by type 2 diabetes mellitus (T2DM) and illustrate the molecular mechanisms potentially involved. The network pharmacology and TMT-based quantitative protomics analysis were conducted to identify potential gene targets of the active ingredients in DM against NAFLD and T2DM. DM was administered to the mice of DM group for 4 weeks, and db/m mice (control group) and db/db mice (model group) were gavaged by normal saline. DM was also given to Sprague-Dawley (SD) rats, and the serum was subjected to the palmitic acid-induced HepG2 cells with abnormal lipid metabolism. The mechanism of DM protection against T2DM-NAFLD is to improve liver function and pathological morphology by promoting peroxisome proliferator-activated receptor γ (PPARγ) activation, lowering blood glucose, improving insulin resistance (IR), and reducing inflammatory factors. In db/db mice, DM reduced RBG, body weight, and serum lipids levels, and significantly alleviated histological damage of liver steatosis and inflammation. It upregulated the PPARγ corresponding to the prediction from the bioinformatics analysis. DM significantly reduced inflammation by activating PPARγ in both db/db mice and palmitic acid-induced HepG2 cells.

Retinal toxicity of long term overdose of sildenafil citrate: A case report.

Purpose: To report a case of eye structure changes in a patient with long-term overdose of sildenafil citrate. Observations: A 28-year-old male presented to our outpatient clinic with flare sensation in both eyes for 1 year after taking sildenafil citrate at a dose of 200 mg daily for two years. mERG and OCT examination revealed persistent damage of retinal photoreceptor cells. The symptoms did not disappear after 3 months off the medication. Conclusions and importance: Long term excessive use of overdose sildenafil citrate can cause serious damage to retinal photoreceptor cells. The retinal side effects of sildenafil citrate still need to be further investigated, and the administration of systemic overdose also needs to be considered by all physicians, not just ophthalmologists.

Protective effects of safranal on diabetic retinopathy in human microvascular endothelial cells and related pathways analyzed with transcriptome sequencing.

Aim: To determine the effect of safranal on diabetic retinopathy in vitro and its possible mechanisms. Methods: We used human retinal microvascular endothelial cells (HRMECs) to test the influence of safranal in vitro. High glucose damage was established and an safranal was tested at various concentrations for its potential to reduce cell viability using the MTT assay. We also employed apoptosis detection, cell cycle detection, a transwell test, and a tube formation assay to look into safranal's inhibitory effects on high glucose damage at various doses. Furthermore, mRNA transcriptome sequencing was performed. mRNA expression levels in a high glucose damage model, a high glucose damage model treated with safranal, and a blank control were compared to find the possible signaling pathway. Western blotting was used to confirm the expressions of several molecules and the levels of phosphorylation in each for the newly discovered pathway. Results: Cell proliferation was inhibited under a high glucose condition but could be protected by safranal at different concentrations (P<0.001). Flow cytometry results suggested safranal also protected cells from apoptosis (P=0.006). A transwell test demonstrated reduced invasiveness of safranal-treated cells in a high glucose condition (P<0.001). In a tube formation investigation, there were noticeably more new branches in the high gloucose group compared to a high glucose treated with safranal group (P<0.001). In mRNA expression patterns on transcriptome sequencing, the MAPK signaling pathway showed an expression ratio. With western blotting, the phosphorylation level of p38-AKT was elevated under a high glucose condition but could be inhibited by safranal. The expression of molecules associated with cell adhesion, including E-cadherin, N-cadherin, Snail, Twist, and fibronectin also changed significantly after safranal treatment under a high glucose condition. Conclusion: Safranal can protect diabetic retinopathy in vitro, and the p38-AKT signaling pathway was found to be involved in the pathogenesis of diabetic retinopathy and could be inhibited by safranal. This pathway may play a role by influencing cell migration and adhesion.

Guideline for the treatment of no light perception eyes induced by mechanical ocular trauma.

Severe mechanical ocular trauma with no light perception (NLP) predicts a poor prognosis of visual acuity and enucleation of the eyeball. Since the innovative treatment concept of exploratory vitreoretinal surgery has developed and treatment technology has advanced, the outcomes of severe ocular trauma treatment in NLP patients have greatly improved. However, there remains a lack of unified standards for the determination, surgical indication, and timing of vitrectomy in NLP eye treatment. To address these problems, we aimed to create evidence-based medical guidelines for the diagnosis, treatment, and prognosis of mechanical ocular trauma with NLP. Sixteen relevant recommendations for mechanical ocular trauma with NLP were obtained, and a consensus was reached. Each recommendation was explained in detail to guide the treatment of mechanical ocular trauma associated with NLP.

CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases.

Blood vessel dysfunction causes several retinal diseases, including diabetic retinopathy, familial exudative vitreoretinopathy, macular degeneration and choroidal neovascularization in pathological myopia. Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefits in most of those diseases, yet unsolved haemorrhage and frequent intraocular injections still bothered patients. Here, we identified endothelial CD146 as a new target for retinal diseases. CD146 expression was activated in two ocular pathological angiogenesis models, a laser-induced choroid neovascularization model and an oxygen-induced retinopathy model. The absence of CD146 impaired hypoxia-induced cell migration and angiogenesis both in cell lines and animal model. Preventive or therapeutic treatment with anti-CD146 antibody AA98 significantly inhibited hypoxia-induced aberrant retinal angiogenesis in two retinal disease models. Mechanistically, under hypoxia condition, CD146 was involved in the activation of NFκB, Erk and Akt signalling pathways, which are partially independent of VEGF. Consistently, anti-CD146 therapy combined with anti-VEGF therapy showed enhanced impairment effect of hypoxia-induced angiogenesis in vitro and in vivo. Given the critical role of abnormal angiogenesis in retinal and choroidal diseases, our results provide novel insights into combinatorial therapy for neovascular fundus diseases.

Inhibition of corneal neovascularization by topical application of nintedanib in rabbit models.

AIM: To evaluate the potential efficacy and mechanisms of nintedanib in corneal neovascularization (NV) in rabbit models. METHODS: Corneal NV was induced using 1 mol/L NaOH. Rabbits (n=21) were randomized to 3 groups: Group 1 were treated with 0.9% NaCl, Group 2 with Avastin (5 mg/mL), and Group 3 with nintedanib (1 mg/mL). All treatments started 1d after alkaline burns and were topically performed 3 times a day for 2wk. Photographs were taken on a slit lamp microscope on day 7 and 14. The NV area, the length of the vascularization and angiogenesis index (AI) were used to evaluate the corneal NV. On day 14, the immunohistochemical (IHC) studies of the cornea were examined. Western blot was performed to test the expression levels of vascular endothelial growth factor (VEGF), Akt, p-Akt, P38, p-P38, MMP-2 and MMP-9. RESULTS: The corneal NV area, vessel length and AI in Group 3 were significantly lower than Group 2, with both being lower than Group 1. IHC staining showed that VEGF was significantly overexpressed in the epithelium and stroma of cornea following alkaline burns. In contrast, the level of VEGF was significantly suppressed in both Group 2 and Group 3. Western blot results further confirmed that, compared with Group 1, Group 3 had significantly reduced expressions of VEGF, Akt, p-Akt, p-P38, MMP-2, and MMP-9 in corneal tissues. Trends of lower levels of MMP-2, AKT, and p-AKT in Group 3 than Group 2 were identified. CONCLUSION: Nintedanib and Avastin can effectively inhibit corneal NV, with P38 MAPK and AKT signaling pathways being possibly involved. Nintedanib seems more effective than Avastin and has the potential to be a novel therapy for preventing corneal NV.

Dendrobium Mixture Ameliorates Diabetic Nephropathy in db/db Mice by Regulating the TGF-ß1/Smads Signaling Pathway.

Dendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the molecular mechanism underlying its action remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-ß1 (TGF-ß1)/Smads signal transduction pathway. Twenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed under a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect the mRNA and protein expression levels of TGF-ß1 and alpha-smooth muscle actin (α-SMA), respectively, in renal tissues. TGF-ß1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. The results showed that DMix significantly reduced the FBG level, BW, KW, and blood lipid level and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced the protein and mRNA expression levels of TGF-ß1 and α-SMA and inhibited Smad2 and Smad3 phosphorylation. We conclude that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-ß1/Smads signaling pathway.

Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing.

AIM: To determine the effects of safranal on choroidal neovascularization (CNV) and oxidative stress damage of human choroidal microvascular endothelial cells (HCVECs) and its possible mechanisms. METHODS: Forty-five rats were used as a laser-induced CNV model for testing the efficacy and safety of safranal (0.5 mg/kg·d, intraperitoneally) on CNV. CNV leakage on fluorescein angiography (FA) and CNV thickness on histology was compared. HCVECs were used for a H2O2-induced oxidative stress model to test the effect of safranal in vitro. MTT essay was carried to test the inhibition rate of safranal on cell viability at different concentrations. Tube formation was used to test protective effect of safranal on angiogenesis at different concentrations. mRNA transcriptome sequencing was performed to find the possible signal pathway. The expressions of different molecules and their phosphorylation level were validated by Western blotting. RESULTS: On FA, the average CNV leakage area was 0.73±0.49 and 0.31±0.11 mm2 (P=0.012) in the control and safranal-treated group respectively. The average CNV thickness was 127.4±18.75 and 100.6±17.34 µm (P=0.001) in control and safranal-treated group. Under the condition of oxidative stress, cell proliferation was inhibited by safranal and inhibition rates were 7.4%-35.4% at the different concentrations. For tube formation study, the number of new branches was 364 in control group and 35, 42, and 17 in 20, 40, and 80 µg/mL safranal groups respectively (P<0.01). From the KEGG pathway bubble graph, the PI3K-AKT signaling pathway showed a high gene ratio. The protein expression was elevated of insulin receptor substrate (IRS) and the phosphorylation level of PI3K, phosphoinositide-dependent protein kinase 1/2 (PDK1/2), AKT and Bcl-2 associated death promoter (BAD) was also elevated under oxidative stress condition but inhibited by safranal. CONCLUSION: Safranal can inhibit CNV both in vivo and in vitro, and the IRS-PI3K-PDK1/2-AKT-BAD signaling pathway is involved in the pathogenesis of CNV.

Inhibition of BAMBI reduces the viability and motility of colon cancer via activating TGF-ß/Smad pathway in vitro and in vivo.

[This retracts the article DOI: 10.3892/ol.2017.6811.].

A novel tri-culture model for neuroinflammation.

Neuroinflammation is believed to play a primary role in the pathogenesis of most neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and schizophrenia. Currently, suitable in vitro neuroinflammation models for studying cellular interactions and inflammatory mechanisms at the neurovascular unit are still scarce. In this study, we established an experimentally flexible tri-culture neuroinflammation model combining murine microglial cells (N11), mouse neuroblastoma Nuro2A cell lines and brain microvascular endothelial MVEC(B3) cells in a transwell co-culture system stimulated with lipopolysaccharides. Neuroinflammation was induced in this tri-culture model as manifested by activated N11 cells via toll-like receptor 4, resulting in increased release of proinflammatory mediators (nitric oxide, interleukin-6 and tumour necrosis factor-α) through the activation of nuclear factor-κB signalling pathway. The released inflammatory cytokines from N11 in turn, damaged the tight junction in microvascular endothelial MVEC(B3) cells, increased permeability of endothelial barrier, and induced tau phosphorylation and up-regulated caspase-3 expression in mouse neuroblastoma Nuro2A cell lines, leading to neuroinflammation injury. In summary, this tri-culture inflammation model mimics the microenvironment, the cellular crosstalk and the molecular events that take place during neuroinflammation. It provides a robust in vitro model for studying neuroinflammation mechanisms and screening for potential therapeutics to treat various neurodegenerative diseases.

Asymptomatic infection by SARS-CoV-2 in healthcare workers: A study in a large teaching hospital in Wuhan, China.

OBJECTIVES: To investigate the proportion and characteristics of asymptomatic infection among healthcare workers (HCWs). METHODS: This study retrospectively investigated 1407 HCWs who were screened for COVID-19 by chest computed tomography (CT) scans and nasopharyngeal swabs for SARS-CoV-2 nucleic acid. Demographics, CT features, nasopharyngeal swabs, baseline symptoms, and laboratory data were collected. RESULTS: Of 1407 HCWs, 235 had symptoms and 1172 were asymptomatic close contacts, of which, 107 were symptomatic cases and 84 were close contacts who had abnormal CT findings. Of 152 symptomatic individuals and 908 close contacts tested for SARS-CoV-2 nucleic acid, 122 symptomatic cases and 38 close contacts had positive reverse-transcriptase real-time polymerase chain (RT-PCR) test results. The rate of confirmed asymptomatic infections was 4.2% (38/908). Both symptomatic and asymptomatic infected cases had high titrations of specific IgG or had ≥four-fold increase in IgG during convalescence compared with the acute phase. Combining the RT-PCR tests and serological findings, the rate of asymptomatic infections was 9.7% (88/908). In terms of the duration of viral shedding, there was no significant difference between symptomatic mild/moderate participants and asymptomatic infections. CONCLUSIONS: The findings demonstrated that a high rate of asymptomatic SARS-CoV-2 carriers existed among healthcare worker close contacts during the outbreak of COVID-19.